The recent advances in our understanding of the molecular basis for a broad range of pediatric diseases, coupled with the legislative changes culminating in the Best Pharmaceuticals for Children Act, has dramatically increased the potential for defining novel therapeutic approaches for a spectrum of childhood diseases. Further, it provides an important opportunity for improving our understanding of how best to utilize medications currently available for children. The Children's Hospital of Philadelphia (CHOP) has the necessary research infrastructure, patient population, and clinical and laboratory expertise to continue its participation and leadership in the Pediatric Pharmacology Research Unit (PPRU) Network. Under the PI leadership of a Board-certified clinical pharmacologist over the past 4 years, the CHOP PPRU experienced impressive growth both in patient accrual to studies and in the development of industry sponsored trials for Network participation. The CHOP PPRU's recruitment of an internationally renowned population pharmacokinetic modeler further increases the depth and strength of this program. The core laboratory has an in depth experience with state-of-the-art analytical techniques allowing for analysis of a broad spectrum of drugs in biologic matrices, each performed according to FDA's Good Laboratory Practices (GLP) specifications. Novel analytical methodologies developed by the CHOP PPRU will allow for ongoing genotype-phenotype correlative studies. The recent establishment of a proteomics core further expands upon these research capabilities. The CHOP PPRU will continue to emphasize clinical pharmacologic trials in the immunocompromised host, the critically ill infant and child, and in pediatric pain management. Two protocols developed for the PPRU Network, "A Pediatric Phase 1 Trial, and Pharmacokinetic, Pharmacogenetic and Pharmacodynamic Study of Dexmedetomidine" and "A Pediatric Population Pharmacokinetic Study of Heparin: Clinical Utility of Exposure and Biomarkers of Anticoagulation" are proposed and highlight CHOP's PPRU scientific focus. Our expertise in drug analytical methods, pharmacokinetic modeling, pharmacogenomics and proteomics, combined with unparalleled pediatric clinical expertise and access to a diverse pediatric population, assure the continued successful participation of the CHOP PPRU in collaborative Network research.